In vitrothermal therapy of AT-1 Dunning prostate tumours

Abstract

To advance the utility of prostate thermal therapy, this study investigated the thermal thresholds (temperature-time) for prostate tissue destruction in vitro. The AT-1 Dunning prostate tumour model was chosen for the study. Three hundred micron thick sections were subjected to controlled temperature-time heating, which ranged from low (40 degrees C, 15 min) to high thermal exposures (70 degrees C, 2 min) (n = 6). After subsequent tissue culture at 37 degrees C, the sections were evaluated for tissue injury at 3, 24 and 72 h by two independent methods: histology and dye uptake. A graded increase in injury was identified between the low and high thermal exposures. Maximum histologic injury occurred above 70 degrees C, 1 min with >95% of the tissue area undergoing significant cell injury and coagulative necrosis. The control and 40 degrees C, 15 min sections showed histologic evidence of apoptosis following 24 and 72 h in culture. Similar signs of apoptosis were minimal or absent at higher thermal histories. Vital-dye uptake quantitatively confirmed complete cell death after 70 degrees C, 2 min. Using the dye data, Arrhenius analysis showed an apparent breakpoint at 50 degrees C, with activation energies of 135.8 kcal/mole below and 4.7 kcal/mole above the threshold after 3 h in culture. These results can be used as a conservative benchmark for thermal injury in the cancerous prostate. Further characterization of the response to thermal therapy in an animal model and in human tissues will be important in establishing the efficacy of the procedure

Supraphysiological Thermal Injury in Different Human Bladder Carcinoma Cell Lines

“…(5) into Eq. (2). The values of the fitted curves agreed well with the experimental data, which indicates the utility of the aforementioned thermal injury model.…”

The Kinetics of Thermal Injury in Human Renal Carcinoma Cells

“…5,38,44 Furthermore, two recent studies on human benign prostatic hyperplasia tissue and rodent prostate cancer tissue in vitro show that the cell injury kinetics measured by membrane integrity vital dye assay and histology (the gold standard for cell injury in tissue) are very similar in their studies. 2,3 Using vital dye as the injury assay allows the heating of cells using a heating stage instead of a water bath, which render the heating process more controllable and may significantly reduce the non-isothermal portion of the thermal insult. 2,3,5 However, it is still important to understand whether the non-isothermal heating is significant in terms of cell injury in thermal therapy, since the peak temperature is very high and the required exposure time for significant cell injury is very short (seconds to minutes) in thermal therapy applications.…”

“…2,3 Using vital dye as the injury assay allows the heating of cells using a heating stage instead of a water bath, which render the heating process more controllable and may significantly reduce the non-isothermal portion of the thermal insult. 2,3,5 However, it is still important to understand whether the non-isothermal heating is significant in terms of cell injury in thermal therapy, since the peak temperature is very high and the required exposure time for significant cell injury is very short (seconds to minutes) in thermal therapy applications. Although cells attached to cell-culture-treated substrate has been dominantly used in studies on thermally induced cell injury, cells suspended in media have also been used to investigate the protein and lipid change in intact cells.…”

Heat shock protein expression and injury optimization for laser therapy design

“…H&E staining was also performed on the irradiated prostate tumors to gain a better understanding of the correlation between temperature and tissue injury associated with laser heating [23]. A lower thermal threshold was observed for destruction of PC3 tumors in vivo compared to their in vitro counterparts under similar conditions due to the presence of the vascular network in vivo as observed by other researchers [39,40]. The HSP expression and injury Fig.…”